Decrease of NAD⁺ Inhibits the Apoptosis of OLP T Cells via Inducing Mitochondrial Fission

Area of Science:

• Immunology
• Cell Biology
• Mitochondrial Dynamics

Background:

• Oral lichen planus (OLP) is a chronic T cell-mediated inflammatory disease.
• Mitochondrial dynamics, specifically fission, are critical for T cell function and fate.
• Nicotinamide adenine dinucleotide (NAD+) is a key regulator of mitochondrial remodeling and cellular energy metabolism.

Purpose of the Study:

• To investigate the role of NAD+ in modulating mitochondrial fission and apoptosis in T cells within the OLP inflammatory environment.
• To explore how NAD+ levels influence mitochondrial structure and function in OLP T cells.

Main Methods:

• Isolation of T cells and plasma from OLP patients.
• Characterization of mitochondrial morphology using electron microscopy and staining.
• Experimental manipulation of mitochondrial fission (Drp1 knockdown) and NAD+ levels (using β-nicotinamide mononucleotide and FK866) in T cells.

Main Results:

• OLP T cells displayed increased mitochondrial fission, evidenced by elevated Drp1 and reduced Mfn2 expression, correlating with decreased apoptosis.
• Reduced NAD+ levels in OLP T cells and OLP plasma-exposed Jurkat cells led to enhanced mitochondrial fission, impaired mitochondrial membrane potential, and reduced respiration.
• Drp1 knockdown in OLP plasma-exposed Jurkat cells increased apoptosis and reduced proliferation.
• NAD+ supplementation reversed these detrimental effects, restoring NAD+ levels, suppressing fission, and promoting apoptosis.

Conclusions:

• Decreased NAD+ levels in OLP T cells contribute to enhanced mitochondrial fission and reduced apoptosis.
• NAD+ supplementation demonstrates potential as a therapeutic strategy to restore T cell homeostasis in OLP by modulating mitochondrial function.